One-year nutrition counselling in the context of a Mediterranean diet reduced the dietary inflammatory index in women with breast cancer: a role for the dietary glycemic index.

Background: the Mediterranean diet, the low dietary glycemic index (GI) and the dietary inflammation index (DII®) have been associated with lower risk of breast cancer (BC) incidence and mortality. Objective: to investigate whether one-year nutrition counselling in the context of a Mediterranean diet, with or without low-GI carbohydrates counselling, may influence the DII in women with BC. Methods: data were obtained from participants of DEDiCa trial randomized to a Mediterranean diet (MD, n = 112) or a Mediterranean diet with low-GI carbohydrates (MDLGI, n = 111). The diet-derived DII and GI were calculated from 7-day food records while Mediterranean diet adherence from PREDIMED questionnaire. Differences between study arms were evaluated through Fisher's exact test or Mann-Whitney test and associations with multivariable regression analyses. Results: Mediterranean diet adherence significantly increased by 15% in MD and 20% in MDLGI with no difference between arms (p < 0.326). Dietary GI significantly decreased from 55.5 to 52.4 in MD and 55.1 to 47.6 in MDLGI with significant difference between arms (p < 0.001). DII significantly decreased by 28% in MD and 49% in MDLGI with no difference between arms (p < 0.360). Adjusting for energy intake (E-DII) did not change the results. Higher Mediterranean diet adherence and lower dietary GI independently contributed to DII lowering (ß-coefficient -0.203, p < 0.001; 0.046, p = 0.003, respectively). Conclusions: DII and E-DII scores decreased significantly after one-year with 4 nutrition counselling sessions on the Mediterranean diet and low GI. Increased adherence to the Mediterranean diet and low GI independently contributed to the DII changes. These results are relevant given that lowering the inflammatory potential of the diet may have implications in cancer prognosis and overall survival.

Ribociclib efficacy in special populations and analysis of patient-reported outcomes in the MONALEESA trials.

INTRODUCTION: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors abemaciclib, palbociclib, and ribociclib radically modified the treatment of hormone receptor-positive/human epidermal growth factor 2-negative advanced breast cancer. Ribociclib efficacy was proved in the phase III MONALEESA-2, -3, and -7 trials. In the first-line setting, ribociclib plus endocrine therapy determined statistically significant improvements in progression-free (PFS) and overall survival (OS) in pre-menopausal (MONALEESA-7) and post-menopausal (MONALEESA-2) women. Likewise, ribociclib and fulvestrant induced a significant PFS and OS benefit in post-menopausal women previously treated with endocrine therapy (MONALEESA-3). Additionally, ribociclib did not affect patients health-related quality of life in all the MONALEESA trials. AREAS COVERED: We reviewed the results of the available randomized phase III trials testing ribociclib and endocrine therapy in advanced breast cancer, focusing on different patient subgroups and then on health-related quality of life. EXPERT OPINION: The benefit of ribociclib is consistent across patient subgroups and is maintained in populations with unfavorable features, such as those with endocrine resistance or visceral metastases. Furthermore, the addition of ribociclib to endocrine therapy delays quality of life deterioration and improves pain scores. These results represent a pivotal improvement for the treatment of advanced breast cancer patients receiving CDK4/6 inhibitors.

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?

BACKGROUND: To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC). OBJECTIVES: The present study assesses, in a real-world setting, the activity of different subsequent therapies in patients who experienced a PD on palbociclib (P) + endocrine therapy (ET), to evaluate the best therapy sequence. METHODS: This is a multicenter retrospective observational study. Records of consecutive HR+/HER2- MBC patients from January 2017 to May 2019 were reviewed. The primary endpoint was the evaluation of progression-free survival (PFS) according to subsequent treatment lines after progression on P+ET. Toxicity data were also collected. RESULTS: The outcomes were analyzed in 89 MBC patients that had progressed on previous P+ET: 17 patients were on hormone therapy (HT) and 31 patients on chemotherapy (CT) as second-line treatments; seven patients were on HT and 34 on CT as third-line therapies. PFS of patients treated with HT as second-line therapy is significantly improved when compared with patients treated with CT (p=0.01). Considering third-line settings, the difference in PFS was not statistically different between HT and CT. A better outcome in terms of toxicity is observed among HT patients for both second- and third-line therapies. CONCLUSIONS: patients who were progressive on P+ET could still benefit from a subsequent ET. In patients who experienced a good efficacy from prior ET, without visceral metastatic sites, HT seems the most suitable option, when compared to CT, also in terms of safety.

Correction: Mediterranean diet and quality of life in women treated for breast cancer: A baseline analysis of DEDiCa multicentre trial.

[This corrects the article DOI: 10.1371/journal.pone.0239803.].

Mediterranean diet and quality of life in women treated for breast cancer: A baseline analysis of DEDiCa multicentre trial.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.

Quality of Life in Women Diagnosed with Breast Cancer after a 12-Month Treatment of Lifestyle Modifications.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer.

BACKGROUND: We reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in 'field-practice' breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs). METHODS: The records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement. RESULTS: Response to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively. At a median follow-up of 16 months (range: 1-55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4-8.6) in the BM group and 8 months (95% CI: 5.7-10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1-6.9) versus 11 (95% CI: 7.1-14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2-15.8) in the BM group and 32 months (95% CI: 24.4-39.6) in the non-BM group (p < 0.0001). CONCLUSIONS: T-DM1 is active in breast cancer patients with BMs.

Eribulin Treatment in Patients with Liver Metastatic Breast Cancer: Eight Italian Case Reports.

Liver metastases are very common in metastatic breast cancer (MBC); current treatments for these lesions are based on systemic chemotherapy, endocrine- or human epidermal growth factor receptor 2 (HER2)-targeted therapy, and palliative therapy. However, no standard approach has been clearly identified for second and further chemotherapy lines in MBC patients. In the phase III clinical trial EMBRACE, eribulin was particularly effective in reducing liver lesions and improving both overall survival and progression-free survival in liver MBC patients. In this series, we collected 8 case reports of Italian clinical practice in which eribulin has shown significant efficacy in reducing liver metastases in MBC patients: complete response was reported in 2 patients, and 4 patients achieved partial response. The treatment was well tolerated, thus confirming that eribulin is a suitable therapeutic option for elderly patients and for those who have metastatic HER2-negative disease. In the setting of MBC, the sequencing of therapeutic agents should consider expected response, side effects, tumor characteristics, and patient's preferences, in order to successfully tailor the most appropriate therapy beyond earlier lines.

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study.

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively. In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatinib.

Low glycemic index diet, exercise and vitamin D to reduce breast cancer recurrence (DEDiCa): design of a clinical trial.

BACKGROUND: Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. METHODS: Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DISCUSSION: DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. TRIAL REGISTRATION: May 11, 2016; NCT02786875 . EUDRACT NUMBER: 2015-005147-14.

Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

The risk of toxicities from trastuzumab, alone or in combination, in an elderly breast cancer population.

BACKGROUND: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. PATIENTS AND METHODS: Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). RESULTS: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. CONCLUSIONS: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring.

Male breast cancer: clinical features and multimodal treatment in a retrospective survey analysis at Italian centers.

AIMS AND BACKGROUND: We report a collection of data about early breast cancer in male patients from 13 Italian institutions. METHODS AND STUDY DESIGN: We obtained data from patient charts and performed statistical analysis. The primary end points were overall survival and disease-free survival. RESULTS: A total of 205 men with invasive breast cancer was identified, with a median age of 66 years. Pathological characteristics were heterogeneous for T stage, N stage and HER2 status. Histological subtype was predominantly ductal infiltrating carcinoma. Most of them were hormone receptor positive. Mastectomy was the most common strategy. Postsurgical treatment was not standardized. Patients with large tumors were more likely to be treated with chemotherapy. Disease recurrence was associated with an ER+ and PR+ status. CONCLUSIONS: We identified a correlation between relapse and hormone receptor expression, as is the case in female breast cancer.